T cell receptor-peptide-major histocompatibility complex interaction (TCR-pMHC)

The T cell receptor (TCR) recognition of tumor peptide-major histocompatibility complex (pMHC) complexes on dendritic cells is the fundamental mechanism by which the adaptive immune system identifies malignant cells [1]. Dendritic cells (DCs) act as professional antigen-presenting cells that capture tumor antigens, process them into short peptides, and present them on MHC molecules to T cells [2]. This interaction, occurring within the immunological synapse, requires the TCR to specifically bind the pMHC complex, providing the primary signal (Signal 1) for T cell activation [1]. In oncology, this process is exploited by therapies such as TCR-engineered T cells (TCR-T) and bispecific T cell engagers (BiTEs), which bypass or enhance natural recognition to direct T cell cytotoxicity against tumors [3]. For instance, drugs like tebentafusp are designed to bridge T cells to specific pMHC complexes on tumor cells, mimicking the natural recognition process [3]. Understanding this interaction is crucial for developing personalized immunotherapies, as it depends on both the patient's HLA type and the presence of specific tumor-associated antigens [4].

Other names

Antigen recognitionTCR-pMHC complexpMHC-TCR interactionImmunological synapse formation

The T cell receptor (TCR) specifically recognizes and binds to a peptide fragment (antigen) presented by a Major Histocompatibility Complex (MHC) molecule on the surface of an antigen-presenting cell like a dendritic cell. This binding event triggers the phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) on the associated CD3 complex, initiating a signaling cascade that leads to T cell proliferation, cytokine production, and cytotoxic activity against the target cell.